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Practical Questions and Answers on the Current Management of Endocrine-Resistant ER+/HER2- Metastatic Breast Cancer

Clinical Thought

As next-generation ER-directed therapies rapidly enter clinical practice, healthcare professionals are faced with evolving questions regarding biomarker testing, interpretation of ESR1 alterations, treatment selection, and management of patients receiving oral endocrine therapies. In this commentary, experts explore emerging evidence and real-world challenges in the use of ESR1 testing and next-generation ER-directed therapies for patients with endocrine-resistant ER-positive/HER2-negative metastatic breast cancer. The discussion highlights practical considerations related to integrating molecular information, evaluating treatment approaches, and addressing safety and adherence considerations in routine care.

Released: July 14, 2026

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Provided by

Provided by Clinical Care Options, LLC dba Decera Clinical Education

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Supporters

Supported by educational grants from Lilly, Rigel Pharmaceuticals, Inc., and Stemline Therapeutics, Inc. 

Lilly

Rigel Pharmaceuticals, Inc.

Stemline Therapeutics, Inc.

Target Audience

This educational activity is intended for medical oncologists, pathologists, nurses, nurse practitioners, pharmacists, physician associates, and other healthcare professionals who care for patients with breast cancer.

 

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Educate patients and colleagues on the mechanisms of action and biologic rationales for using next-generation SERDs in endocrine-resistant ER-positive/HER2-negative ABC

Financial Disclosures

Primary Author

Mabel Mardones, MD: consultant/advisor/speaker: AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly Medical, Menarini, Novartis, Pfizer.

Joyce O’Shaughnessy, MD: consultant/advisor/speaker: AADI Bioscience, Agendia, Amgen, Aptitude, AstraZeneca, BioNTech, Bristol Myers Squibb, Daiichi Sankyo, Duality, Eisai, Ellipses, Exact Sciences, G1 Therapeutics, Genentech, Gilead, Guardant Health, HiberCell, Jazz, Johnson & Johnson, Lilly, Menarini/Stemline, Merck, Mersana, Natera, Novartis, Pfizer, Pierre Fabre, Puma, RayzeBio, Roche, Sanofi, Seagen, Stemline, Summit, Tempus, TerSera.

Michelle Shiller, DO: consultant/advisor/speaker: AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Lilly, Merck, Pfizer, RevMed, Roche.